TLC178 designated by US FDA as drug for rare paediatric disease in the treatment of Rhabdomyosarcoma

[COMMENT: This came through the wire today. If anyone has additional information, please post it in the comments section. Thank you. Alan]

Taiwan Liposome Company, Ltd.,(TLC) (4152:TT) today announced that its oncology drug candidate TLC178 has been designated as a drug for a rare pediatric disease in the treatment of rhabdomyosarcoma (RMS) by the U.S. Food and Drug Administration (FDA).

This designation brings the company closer to receiving a Rare Pediatric Disease Priority Review Voucher, which can be used to expedite the review process or transferred to another company.

Rhabdomyosarcoma (RMS) is an aggressive and highly malignant form of cancer that develops from skeletal muscle cells that have failed to fully differentiate. RMS predominantly afflicts children. More than half of patients diagnosed with RMS are younger than 10 years of age and RMS accounts for approximately three to four percent of all cases of cancers diagnosed in childhood. About 350 new cases of RMS occur each year in the U.S.

RMS patients are typically treated with surgery to remove tumor tissue, which is followed by chemotherapy to decrease recurrence. Vincristine is currently the most common chemotherapeutic therapy for RMS. Vincristine is a vinca alkaloid similar to vinorelbine.

TLC178 consists of vinorelbine encapsulated using the NanoXTM nanotechnology platform to provide an improved safety profile relative to vinorelbine alone. Studies using preclinical models have demonstrated promise for TLC178 in the treatment of RMS.

The FDA’s Office of Orphan Products Development has designated TLC178 (vinorelbine tartrate liposome injection) for the treatment of RMS as a drug for a rare pediatric disease.

This designation may lead to an award of a priority review voucher, which can be redeemed to receive a priority review of a subsequent marketing application for a different product or sold to another company. A priority review voucher can shorten the FDA review process from at least ten months to six months.

A Phase 1/2 dose-escalation study of TLC178 is currently underway at sites in Taiwan and in the U.S. to evaluate the maximum tolerated dose (MTD). Once established, the MTD will be used in pivotal studies.

One of the most frightening words a patient can hear from a doctor is “cancer.” We know it from the experience of our families and friends, and the millions of Americans who hear it directly from their doctors each year.

In President Barack Obama’s final State of the Union address, he compared the effort required to eradicate cancer to a “moonshot,” summoning the American ingenuity and scientific pursuits that sent humankind to the moon. We believe that it’s time for a full and complete national commitment to rid the world of this disease, because the truth is that ending cancer as we know it is finally within our grasp.

A key element of the cancer moonshot is to incentivize more cooperation between the government and the private sector. We recognize that while the U.S. government has tremendous resources at its disposal, we also know a lot of our best expertise exists outside the government, within the private medical and research community. There is little doubt that this will be the site of the next big breakthroughs in cancer treatment. We know it because we’ve seen it at the world’s best cancer research centers across America, led by the world’s greatest cancer doctors, researchers and philanthropists -- many of whom we’ve met with over the last few months.

To that end, and in support of the cancer moonshot, we are thrilled that Johns Hopkins University will create the Bloomberg-Kimmel Institute for Cancer Immunotherapy, thanks to private grants of $125 million. This new institute will build on the school’s groundbreaking work in immunotherapy, one of the most promising avenues of research today.

Led by Dr. Drew Pardoll and funded in partnership with the philanthropist Sidney Kimmel, the institute will support the same scientists who performed some of the first clinical trials of immunotherapy agents known as checkpoint blockade inhibitors. These agents interfere with molecules that shield tumor cells from the body’s immune system. In fact, two of these inhibitors have already been approved by the FDA for use against lung cancer and melanoma, and show promise across almost every cancer.

Discoveries like these inhibitors are what will ultimately make it possible to cure cases of cancer that might have been hopeless just a few short years ago. We know that there’s no silver bullet, and no one expects it to happen overnight. But the truth is that because of exciting advances in science and technology over the last 10 years, we are far closer to major breakthroughs than many people realize.

With the right partnerships, we can bolster the incredible work that is already occurring among immunologists, geneticists and other scientists with new innovations from the technology sector. Recently, an entire industry has sprung up with the power to process medical and scientific information on a massive scale. This computing power is already allowing researchers to accelerate their progress like never before. By aggregating big data from cancer studies in one central location that’s accessible to scientists, researchers and physicians, we can further speed up advances in research.

With the cancer moonshot and public-private partnerships, we are not trying to make incremental change. We’re looking to make quantum leaps. Our goal is to make a decade’s worth of medical advances in the next five years. And with new institutions working together and new resources dedicated to the problem, we know we can finally gain the upper hand on a disease that has already robbed the world of far too much talent and love.

The original mission to the moon was a government-led, -directed and -funded initiative. The cancer moonshot will be a true partnership between government, the private sector, academia and the philanthropic community. It has the potential to save millions of lives.

It could prove to be a model for how public-private partnerships can overcome even the most difficult challenges. And it could turn cancer from a death sentence into a chronic, manageable disease -- or in many cases, a curable one -- for millions of people around the world.

Cancer thrives by mutating. But sometimes, a mutation leaves it vulnerable

[COMMENT: This is an interesting read albeit not specific to Rhabdo. I have, for a long time, been an advocate of multiple biopsies (time-line studies) so that our clinicians and researchers can have a better indication of the efficacy of their treatment in 'near real time' - a window into the life of the tumor, so to speak. While I understand the dangers of any additional surgical procedure, I also understand that the beast we're fighting - Rhabdomyosarcoma - can be far more dangerous. The idea that drug resistance can turn itself around is so very interesting.

Any thoughts in our community? (Alan)]

Cancer treatment is like an arms race. After a tumor evolves resistance to one drug, doctors switch to another therapeutic weapon — and on and on, until the tumor is vanquished or the drug cupboard is bare.

But a case study published Wednesday in the New England Journal of Medicine suggests this steady battle march can sometimes swing around on itself.

That’s what happened to a 52-year-old woman with advanced lung cancer. Her tumor cells mutated in such a way that they once again became vulnerable to the medication she’d taken early in her fight, even though her cancer had previously evolved resistance to that drug.

The new findings suggest that doctors might do well to take repeated biopsies to check how a patient’s tumor cells are evolving and to consider revisiting the drugs they used at the start of the battle — because those drugs can sometimes have a second life.

“It’s really amazing,” said Dr. Gregory Riely, a lung cancer specialist at the Memorial Sloan Kettering Cancer Center who was not involved in the woman’s treatment.

“This is the first time clinically that we’ve seen a cancer mutate in such a way that it again becomes sensitive to a targeted therapy,” Riely said. “The typical resistance pattern is a straight line … with mutations developing along the way. These data suggest that we may be able to turn that around and make it a circle.”

Dr. Alice Shaw, an oncologist at Massachusetts General Hospital, diagnosed the patient in 2011 with an advanced form of lung cancer fueled by a cancer-causing enzyme called ALK. The woman, who never smoked, started taking the Pfizer drug Xalkori, which specifically targets ALK. At first, it seemed to work.

But after 18 months of treatment, scans revealed that her cancer was growing again. It had spread to lymph nodes in her abdomen. And a biopsy revealed a mutation that rendered her cancer immune to the drug.

The woman tried another ALK-inhibitor (a Novartis drug called Zykadia) plus a less targeted experimental agent, but neither therapy worked. After lesions cropped up in her liver, it became clear that the patient needed to try something else. Last year, she enrolled in a Phase 1 trial of a new ALK-blocker from Pfizer called lorlatinib.

The drug worked — at least at first. Initial scans showed a 41 percent reduction in tumor size, and the woman did well for about nine months. But as often happens, the cancer mutated again. This latest drug became useless, as well.

Then came the twist: Genetic testing revealed that the very same mutation that conferred resistance to lorlatinib actually made the tumor vulnerable again to the first anticancer drug the woman had taken. The patient went back on Xalkori, and for the next six months her tumors shrank and her liver function improved.

She eventually succumbed to the disease, but she defied expectations. Most patients with advanced lung cancer die within a year. This woman survived for four.

In cancer treatment today, biopsies are often taken only once, to establish a diagnosis and determine an initial course of therapy.

Shaw said her patient’s case highlights the need to biopsy repeatedly during treatment and tailor drug regimens accordingly. This is becoming increasing necessary, she said, as cancer therapies become more precise, targeted, and personalized.

“These biopsies are really critical in revealing mechanisms of resistance,” Shaw said, “and they can sometimes reveal some surprising mechanisms that may actually make you rethink the use of drugs that you wouldn’t have thought of before.”

Shaw published the case report along with her colleagues at Mass. General and scientists at Pfizer.

Elie Dolgin can be reached at elie.dolgin@statnews.com
Follow Elie on Twitter @eliedolgin

It’s time for Congress to reinvest in cancer research

Research funded by the National Institutes of Health (NIH) is the basis for the most important cancer breakthroughs of our time, but it is threatened by more than a decade of inadequate federal funding. Backing research on cancer, a disease that touches almost every American, should be a top priority as Congress will soon decide on how to allocate $25 billion in additional non-defense discretionary spending for fiscal year 2016.

Every cancer survivor is living proof that medical research saves lives, and this is not a time to reduce our investment in cancer research. As our population ages, cancer is expected to become the leading cause of death in the U.S. by 2030.

Over the past decade, federal funding for the National Cancer Institute (NCI) has decreased by 20 percent, once inflation is taken into account. These cutbacks are affecting our nation’s research enterprise, our scientific leadership in the world and, most importantly, people living with cancer. Promising research is going unfunded, new studies are being delayed or scaled back, and fewer cancer patients have access to clinical trials. In just the past four years, between 2010 and 2014, the number of patients enrolled in NCI’s clinical trial network decreased by almost 25 percent. The funding environment is so bleak that a growing number of cancer researchers are leaving the field altogether.

NIH has a particularly important and unique role to play as we accelerate the use of precision medicine to fight cancer. Precision medicine involves identifying unique molecular and genetic drivers of cancer and developing treatments that target them. This can result in more effective treatments with fewer side effects. One important discovery during my career has been pathway targeted agents such as imatinib for chronic myelogenous leukemia (CML) which targets the bcr-abl pathway and ibrutinib which targets the Bruton’s Tyrosine Kinase (BTK) pathway in chronic lymphocytic leukemia (CLL) cells. Both of these directed agents are orally administered, have minimal side effects in most patients, and provide marked improvements in outcomes in these patient populations.

Only leadership and investment from the federal government can make precision medicine the norm. Some may assume that as public funding for cancer research wanes, the private sector will pick up the slack. But that simply isn’t the case. The NIH supports critical studies that the private sector has little incentive to conduct, such as basic research and trials comparing the effectiveness of already-available treatments, combining therapies developed by different companies, researching drugs for pediatric and rare cancers, and understanding the toxicity of the treatments. These and other NCI-funded studies yield essential insights that make the private sector’s cancer research, drug development and commercialization possible.

In the late 1990s, with bipartisan support, Congress voted to double the NIH budget over five years. The investment greatly accelerated the pace of scientific discovery. Now we need Congress to show that same kind of bold leadership. Providing NIH with $32 billion would make up for roughly three years of inflation, but we still have a long way to go. Congress can help NIH to recover from a decade of neglect by providing the highest possible increase in fiscal year 2016 funding for the NIH, including a proportional boost for the NCI. Our nation’s cancer researchers, doctors, and patients are relying on the federal government to drive the next generation of progress to save lives. With new resources, the NIH will be able to capitalize on the promise of precision medicine and other critical scientific opportunities and give new hope to all those affected by cancer.

Vose is president of the American Society of Clinical Oncology (ASCO). Founded in 1964, ASCO is the world’s leading professional organization representing physicians who care for people with cancer.

Metastatic Rhabdomyosarcoma: Still Room for Improvement

Of the approximately 400 children and adolescents diagnosed each year in the United States with rhabdomyosarcoma, between one in five and one in six will be considered high-risk patients by virtue of the presence of one or more sites of distant metastatic disease, most commonly involving lymph nodes, bones, bone marrow, and the lungs. These patients tend to be disproportionately older, of male sex, and have alveolar histology, and most present with bulky tumors (> 5 cm). Typically, though, even in patients with widespread disease, these bulky tumors respond promptly and dramatically to any number of chemotherapy regimens. It is not unusual for patients who present with extensive disease to achieve complete, or near-complete, radiographic responses within 3 to 6 months from the start of systemic therapy. Indeed, in the First Intergroup Rhabdomyosarcoma Study that opened in 1972, fully three quarters of patients with metastatic rhabdomyosarcoma achieved either a complete (50%) or partial (25%) response within 15 weeks of therapy that would, by modern standards, be considered mild.1 The challenge for this population, generally, is not eradicating macroscopic disease visible at the time of diagnosis but, rather, preventing the recurrence of occult disease that is invariably still present at the completion of therapy. Curative front-line therapy is administered to no more than one third of newly diagnosed patients with high-risk rhabdomyosarcoma, with most patients experiencing relapses within 24 months of diagnosis, and with few patients surviving more than 3 years after experiencing relapse. Unfortunately, over the past four decades, intensification of therapy through five generations of United States-led cooperative group clinical trials under the auspices of the Intergroup Rhabdomyosarcoma Study Group and its successor, the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (COG), has produced no meaningful improvement in outcome for the vast majority of patients with metastatic rhabdomyosarcoma.2-6

In the article accompanying this editorial, Weigel et al7 report the final results of the most recently completed COG clinical trial, ARST-0431, for patients with high-risk rhabdomyosarcoma. This 54-week treatment regimen builds on the striking activity and relatively favorable toxicity profile of the combination of vincristine and irinotecan in preclinical8 and phase II window testing6 in newly diagnosed patients with metastatic rhabdomyosarcoma. In addition, the regimen uses filgrastim in an attempt to maximize alkylator dose intensity by administering standard doses of the other agents at reduced intervals of 2 weeks. ARST-0431 enrolled 109 patients with stage IV (metastatic) rhabdomyosarcoma during a 23-month period. Of those patients enrolled, 80% received irinotecan once per day for 5 days. Radiation of the primary site was generally delayed until after approximately 6 months of treatment, and selective irradiation of sites of metastatic disease was encouraged. Surgical resection of the primary site was generally not recommended unless it would significantly reduce the radiation field (or for palliation). The primary objective was to improve 3-year event-free survival (EFS) to 55%, representing a 60% reduction in the risk of treatment failure compared with standard multiagent therapy. As expected, more than half of patients were older than 10 years and had large, predominantly alveolar tumors, and more than half also had regional nodal involvement in addition to distant metastatic disease. Fewer than 20% of patients were younger than 10 years with embryonal rhabdomyosarcoma. Furthermore, it was determined, using a prognostic risk-classification schema developed from a pooled international analysis of patient outcomes for metastatic rhabdomyosarcoma,9 that approximately 60% of patients had two or more risk factors—a group for whom long-term outcome has been particularly grim.

Unfortunately, the results of this trial proved to be as disappointing as previous results. With a median follow-up time of more than 3.5 years for surviving patients (minimum, 7.7 months), patients experienced a 3-year EFS of 38% and an overall survival of 56%. For patients with alveolar rhabdomyosarcoma (the majority of the patients enrolled onto the study), 5-year EFS was 16% (range, 8% to 28%), and 5-year EFS was essentially identical, at 19%, for patients with an Oberlin risk score of ≥ 2. The best outcome was seen in the relatively small proportion of children younger than 10 with embryonal rhabdomyosarcoma (< 20% of the total patient population) whose 3-year EFS of 60% is comparable to the outcome of patients with nonmetastatic, intermediate-risk rhabdomyosarcoma.10 Though not unanticipated, toxicity was substantial: with the exception of the first 6 weeks of vincristine and irinotecan window therapy, febrile neutropenia, with or without documented infection, occurred in well over half of patients; treatment delays, rare in the beginning weeks of therapy, became common during the middle portion of therapy concurrent with the administration of radiation therapy. What, then, can we learn from this study? The good news, though limited, is that outcome for the relatively small number of younger children with embryonal rhabdomyosarcoma and limited metastatic disease (generally lung only) is substantially better than that for all other patients with metastatic rhabdomyosarcoma. Whether these children will maintain the same excellent outcome with significant de-escalation in alkylator exposure planned in the next COG trial for other intermediate-risk patients is uncertain. For the majority of other patients—the too-high number of those who will die prematurely—the outcome was not unexpected. For more than 25 years, pediatric oncologists have prayed at the altar of the goddess of dose intensity and have walked away largely empty handed. This lack of benefit is not confined to patients with metastatic rhabdomyosarcoma, however, as the same observation has been made of patients with metastatic Ewing sarcoma, desmoplastic small round-cell tumor, and osteosarcoma.11-13
Because the status quo remains unacceptable, where, then, do we begin to look for answers? First, basic scientists and clinicians must leave their silos and be afforded regular opportunities to meet and collaborate with each other. Such efforts have begun and must intensify.14 Our ability to develop clinically relevant targeted therapies against rhabdomyosarcoma has thus far been outstripped by our insights into its biology,15,16 but our collaborative efforts must continue, and funding to support them cannot depend only on the philanthropic generosity of families that have been scarred eternally by the loss of a loved one to rhabdomyosarcoma. Second, as has already begun, well-designed clinical trials of hypothesis-driven, biologically targeted therapies must continue. Though the earliest of these trials failed to achieve the enormous promise that two decades of preclinical research had suggested,17,18 more recent trials have achieved positive results.19
Finally, we must recognize that metastatic rhabdomyosarcoma is not the same biologic entity as nonmetastatic rhabdomyosarcoma. For the latter group of patients comprising the majority of children with rhabdomyosarcoma, local relapse remains the dominant form of treatment failure, and treatment strategies aimed at optimizing local control rates while minimizing long-term morbidity are considered paramount. Conversely, for patients diagnosed with metastatic rhabdomyosarcoma, the inability to eradicate occult microscopic residual disease remains the overwhelming challenge. Whether by targeting genetically quiescent cells20 with the administration of longer-duration maintenance therapy in patients with minimal residual disease,21 or by focusing on drug-development strategies that specifically target the metastatic process,22,23 newer treatment paradigms are desperately needed if we are to end the well-intentioned but failed efforts of the past four decades.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Metastatic Rhabdomyosarcoma: Still Room for Improvement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.
Leonard H. Wexler - Consulting or Advisory Role: AstraZeneca

The Game of Battleship and the Battle Against Rare Pediatric Cancers
Alan R. Ehrlich, Chair, Focus on Rhabdo

The game Battleship has been around for almost a century, starting off as a simple, two-player paper and pencil game requiring nothing more than each player drawing a 10x10 grid on piece of paper and positioning their fleet, usually one aircraft carrier, one battleship, one submarine, two destroyers and two PT boats, on the grid by coloring in the boxes representing the warships.

The players would take turns attempting to ‘discover’ the locations of their opponent’s ships. They would call out a grid location (e.g., C-5, F-9) and their opponent would indicate whether they had a hit or miss.

I played the game a lot as a child. Often, to make the game more exciting, we would expand the grid to 20x20, thus expanding the ‘ocean’ from 100 squares to 400. The game took a lot longer to play and scoring a ‘hit’ was far more challenging. Admittedly, expanding the grid made locating the ships and scoring a hit rather frustrating.

Today’s search for cures for rare childhood cancers reminds me a lot of the old Battleship game - only the grid is exponentially larger, there are a large number of players and the stakes involved are the lives of our most vulnerable children. In this highly sophisticated adaptation of the game, rather than calling out the coordinates of a square and getting a hit or miss response, scientists claim their squares by researching a scientific hypothesis with the hope that they will score a hit that will move them one step closer to sinking the ‘cancer’ ship.

While discovery has and continues to provide important insight, by its nature it cannot connect the dots in a way that would provide a complete and accurate picture of the RMS growth - decay - relapse cycle - without which the path to a cure remains both circuitous and distant.

If the Battleship game were played by today’s sophisticated youths, guessing grid coordinates would be replaced by easily obtainable data. The players would be flying drones high above the competition, taking and studying high-definition images laced with GPS data, measuring ocean temperatures, getting local depth soundings and estimating the speed and direction of the local ocean currents. Stealth recon drones would be deployed to track any movement of the fleet and provide information on the number on sailors deployed on each ship and what the mess hall was serving for dinner that night…
…all before a single coordinate was called or a hit or miss response recorded.

Having enough of the right data, correctly analyzing it, and creating and implementing a strategic attack dramatically increases the chance of a successful encounter.

In an article titled “MicroRNA and pediatric tumors: Future perspectives”, published online in Acta Histochemica on 9 March 2015, Galino et al wrote “A better understanding of pediatric tumor biology is needed to allow the development of less toxic and more efficient therapies, as well as to provide novel reliable biomarkers for diagnosis and risk stratification.” [R Gulino, S Forte, R Parenti, L Memeo, M Gulisano, 2015]

With the technological advances that have been made in the last few decades we should have a clear understanding of the tumor biology of even rare pediatric cancers, yet it remains an elusive goal. To gain this understanding we need to move away from the singular use of scientific discovery to a more disciplined and focused “Big Data” approach - creating a database of all relevant patient (and family) information (e.g., DNA, RNA, protein assays, etc.) taken in a consistent manner across the disease progression time-line and then providing grants for a deep analysis of the data.

Would we have a better understanding of the disease if we could analyze the DNA found within the initial tumor to that found outside of the clear margins? The DNA of the initial tumor to that found in the tumor after 4 weeks of chemo? After 20 weeks of chemo? Within the primary tumor area during remission? Against the DNA found in a relapse tumor at the primary site and tumor cells in the metastatic areas? And sadly, but critically important, the DNA from tumor sites and clear sites taken during autopsy should the patient not survive their bout with rhabdo.

Would our understanding of the disease increase if we could do the same for RNA and the various proteins in and around the tumor site(s).

Having this information for, let’s say, 100 RMS patients, would provide a rich database that can be analyzed, synthesized and dissected; various aspects of the disease progression can be compared across multiple patients; and the effects of the disease and the treatment protocol can be analyzed along both the individual’s time-line and a multi-patient time-line - providing a much clearer understanding of the disease pathology.

This certainly opens up a number of ethical, legal, financial and process issues all of which can be answered as we move forward. Most importantly, this singular question must be asked: Are we endangering the lives of those diagnosed with RMS in the future by not aggressively researching all aspects of the disease today, using the only source that we have - the current RMS patients? The data collected would be an incredible gift - given with love and respect - from one generation of patients to those forthcoming.

I want to thank Dr. Hayes-Jordan for an excellent and informative webinar on Clear Surgical Margins and the HIPEC procedure (22 June 2014). I will be posting the video of the program in a few days (we experienced some technical difficulties that needs to be edited out). You can access the video of this webinar by clicking here. Note that you must be logged onto the website to view the video.

Dr. Hayes-Jordan offered to answer any questions that Focus On Rhabdo members might have (general questions only, she cannot answer questions regarding specific medical conditions). This is the place to ask those questions. Please use the comment box on the bottom

Imagine that there was an anti-cancer agent that had the all-time best response against rhabdomyosarcoma, particularly alveolar rhabdo, of ANY single agent EVER tested in the Pediatric Preclinical Testing Program. Imagine that all four alveolar rhabdo cell lines tested obtained a complete response in mouse xenografts. Imagine that this agent was just a couple of IV shots, and when tested in a pediatric Phase 1 clinical trial was found to be relatively safe. Then imagine that the agent stopped being produced because results in adult cancers were disappointing, and the planned Phase 2 trial in children was never done to find out how effective this agent was.

Unfortunately, this isn’t an imaginary situation. It describes what happened to NTX-010, the oncolytic virus also known as Seneca Valley Virus. For details on how effective it was in the preclinical studies, see the story here.

But imagine if we could find a source of funding to start manufacturing this again and continue the testing. Thoughts? Worth trying?

]]>http://focusonrhabdo.org/seneca-valley-virus-study-can/feed/5496Is it my imagination or are we seeing more Rhabdo cases in ‘older’ individuals?http://focusonrhabdo.org/imagination-seeing-rhabdo-cases-older-individuals/
http://focusonrhabdo.org/imagination-seeing-rhabdo-cases-older-individuals/#commentsFri, 21 Mar 2014 12:39:56 +0000http://focusonrhabdo.org/?p=428

We all know that Rhabdomyosarcoma is classified as a childhood cancer. It seems to me that we have been hearing more and more about cases of Rhabdo in older - teens and young adults - individuals. Most treatment protocols are based on childhood cases and provided in the children's area of the hospital.

Is this something that we - our Scientific Advisory Council - should be looking into?